%0 Journal Article
%A Riccardi, Laura
%A Nguyen, Phuong
H.
%A Stock, Gerhard
%D 2012
%T Construction of the Free
Energy Landscape of Peptide
Aggregation from Molecular Dynamics Simulations
%U https://acs.figshare.com/articles/journal_contribution/Construction_of_the_Free_Energy_Landscape_of_Peptide_Aggregation_from_Molecular_Dynamics_Simulations/2532373
%R 10.1021/ct200911w.s001
%2 https://acs.figshare.com/ndownloader/files/4175374
%K Free Energy Landscape
%K dynamics simulation
%K product basis
%K Molecular Dynamics SimulationsTo
%X To describe the structure and dynamics of oligomers during
peptide
aggregation, a method is proposed that considers both the intramolecular
and intermolecular structures of the multimolecule system and correctly
accounts for its degeneracy. The approach is based on the “by-parts”
strategy, which partitions a complex molecular system into parts,
determines the metastable conformational states of each part, and
describes the overall conformational state of the system in terms
of a product basis of the states of the parts. Starting from a molecular
dynamics simulation of n molecules, the method consists
of three steps: (i) characterization of the intramolecular structure, that is, of the conformational states of a single molecule
in the presence of the other molecules (e.g., β-strand or random
coil); (ii) characterization of the intermolecular structure through the identification of all occurring aggregate
states of the peptides (dimers, trimers, etc.); and (iii) construction
of the overall conformational states of the system
in terms of a product basis of the n “single-molecule”
states and the aggregate states. Considering the Alzheimer β-amyloid
peptide fragment Aβ16–22 as a first application,
about 700 overall conformational states of the trimer (Aβ16–22)3 were constructed from all-atom molecular
dynamics simulation in explicit water. Based on these states, a transition
network reflecting the free energy landscape of the aggregation process
can be constructed that facilitates the identification of the aggregation
pathways.
%I ACS Publications